Fig 1.
Basal vascular supply (1), angiographic study (2), and surgical view of the basal circulatory anastomosis (3) in the common pig.
The most relevant arteries in the pig are shown in the angiographic study. Note that the animal presents a network of small bilaterally interconnected vessels called rete mirabile, the site from which the internal carotid artery originates intracranially. Rete mirabile are perfused on both sides by the ascending pharyngeal artery, which originates from the common carotid artery. In contrast to humans, it should be noted that in each hemisphere 2 middle cerebral arteries (MCAs) emerge from the internal carotid arteries, 1 coursing laterally and the other rostrally (the latter provides vascularization to the olfactory tract).
Fig 2.
Two representative 5-mm brain coronal slices from animal #3 stained with 1% 2,3,5-Triphenyltetrazolium chloride (TTC) solution and showing the ischemic core at 7.5 h after left MCA occlusion.
Note how with TTC staining the entire territory of the left MCA (i.e. the infarcted territory) remains a pale cream or white color, while the non-infarcted viable brain stains red or pink. In this particular case, the entire MCA territory was affected, including the 3 MCA sub-territories (deep, superficial anterior, and posterior). The deep territory of the MCA includes the caudate nucleus, the internal and the external capsules, the preoptic area, and the hypothalamus.
Table 1.
Ischemic period and infarct volume in pig specimens.
Table 2.
Metabolite values and PtiO2 measurements in the entire animal group during basal and ischemic periods in CORE and PENUMBRA.
Fig 3.
The representative pattern of microdialysis values in the ischemic core and in the penumbra of animal #5.
We used PtiO2 data from animal #2 to represent the PtiO2 drop after clipping both MCAs because the probe had been misplaced outside the core in animal #5 (image not shown) and because baseline data was missing in some of the remaining animals. The increase in PtiO2 in the first 2 hours may be explained by the running time of PtiO2 probes. The clip illustrated at the top of the diagram shows the time in which clipping of both MCAs was carried out. PtiO2 data in animal #2 was consistent with the typical PtiO2 profile observed in all but 1 animal (#5). In the ischemic core, a rapid decrease in [Glu]brain was observed after occlusion, followed by a significant drop in [Pyr]brain and a significant increase in [Lac]brain and in the lactate/pyruvate ratio (LPR). LPR values 2 hours after clipping could not be calculated because [Pyr]brain levels were undetectable and therefore LPR rose to infinite values. A significant increase in [Pyr]brain was also observed in the core, reaching a plateau at 5 h post-ischemia. In the penumbra area, [Lac]brain and the LPR values also increased, but they were not as pronounced as in the core. [Pyr]brain levels were unstable in the penumbra and at 4 to 7 h after clipping followed the same pattern as [Glu]brain. Glycerol also increased in the penumbra, reaching levels well above those observed in the samples taken from the core.
Table 3.
Ionic data of the extracellular space in both monitored brain areas.
Fig 4.
SUR1 expression in astrocytes, neurons, and capillary endothelial cells.
The figure shows fluorescent double labeling for GFAP (panel A), NeuN (panel B), CD31 (panel C) and SUR1 in the core and penumbra regions. The most lateral column on the right shows the merged images of the controls (i.e. contralateral healthy tissue). Original magnification = 20×(A) and 40× (B, C). Nuclei were counterstained with DAPI. All tissue sections were obtained from animal #5 7 hours after ischemia onset.
Table 4.
Expression of SUR1 and TRPM4 in neurons and vessels.
Results are shown as median (min–max) of the percentage of SUR1/TRPM4-positive neurons and vessels versus the total number in these 2 cell types.